Department of Radiotherapy, Medical University of Lodz, Lodz, Poland.
Department of External Beam Radiotherapy, Copernicus Memorial Hospital in Lodz Comprehensive Cancer Center and Traumatology, Lodz, Poland.
Front Immunol. 2024 Aug 1;15:1426635. doi: 10.3389/fimmu.2024.1426635. eCollection 2024.
Radiation induced lymphopenia (RIL) deteriorate survival and diminishes the benefit of immune checkpoint inhibitors in combined treatment of lung cancer. Given the inconsistent data across various studies on the predictors of RIL, we aim to methodically elucidate these predictors and formulate a practical guide for clinicians.
We conducted observational cohort study in four tertiary cancer centers. Patients with non-small cell lung cancer and small cell lung cancer, without lymphopenia grade >1, who underwent standalone radiotherapy (RT) in minimum 15 fractions were eligible. Dose-volume parameters of structures and clinical factors were comprehensively analyzed using various predictors selection methods and statistical models (Linear Regressors, Elastic Net, Bayesian Regressors, Huber Regression, regression based on k-nearest neighbors, Gaussian Process Regressor, Decision Tree Regressor, Random Forest Regressor, eXtreme Gradient Boosting, Automated Machine Learning) and were ranked to predict lymphocytes count nadir (alc_nadir).
Two hundred thirty eight patients (stage I-3.4%, II-17.6%, III-75.2%, IV-3.8%) who underwent RT to median dose of 60 Gy were analyzed. Median alc_nadir was 0.68K/mm. The 60 feature sets were evaluated in 600 models (RMSE 0.27-0.41K/mm). The most important features were baseline lymphocyte count (alc_1), mean lung_dose, lung v05, lung v10, heart v05 and effective dose to immune cells (edic). In patients with alc_1 ≤ 2.005K/mm, median alc_nadir predictions were 0.54K/mm3 for lung_v05p > 51.8% and 0.76K/mm for lung_v05p ≤ 51.8%. Lymphopenia was rare in patients with alc_1 > 2.005K/mm.
RIL was most severe in patients with low early lymphocyte counts, primarily triggered by low RT doses in the heart and lungs.
放射性淋巴细胞减少症（RIL）会降低生存质量，并削弱肺癌联合免疫检查点抑制剂治疗的获益。鉴于不同研究中 RIL 的预测因素数据不一致，我们旨在系统地阐明这些预测因素，并为临床医生制定实用指南。
我们在四个三级癌症中心进行了观察性队列研究。符合条件的患者为非小细胞肺癌和小细胞肺癌患者，无 1 级以上的淋巴细胞减少症，且接受至少 15 次分割的单纯放疗（RT）。使用各种预测因素选择方法和统计模型（线性回归器、弹性网络、贝叶斯回归器、Huber 回归、基于 K-最近邻的回归、高斯过程回归器、决策树回归器、随机森林回归器、极端梯度提升、自动化机器学习）全面分析了结构和临床因素的剂量-体积参数，并对预测淋巴细胞计数最低值（alc_nadir）的因素进行了排名。
对 238 名接受中位剂量为 60 Gy RT 的患者（I 期-3.4%，II 期-17.6%，III 期-75.2%，IV 期-3.8%）进行了分析。中位 alc_nadir 为 0.68K/mm。对 60 个特征集在 600 个模型中进行了评估（RMSE 为 0.27-0.41K/mm）。最重要的特征是基线淋巴细胞计数（alc_1）、平均肺剂量、肺 v05、肺 v10、心脏 v05 和免疫细胞的有效剂量（edic）。在 alc_1≤2.005K/mm 的患者中，如果肺 v05p＞51.8%，则中位 alc_nadir 预测值为 0.54K/mm3，如果肺 v05p≤51.8%，则中位 alc_nadir 预测值为 0.76K/mm。在 alc_1＞2.005K/mm 的患者中，淋巴细胞减少症很少见。
早期淋巴细胞计数低的患者 RIL 最严重，主要由心脏和肺部的低 RT 剂量引起。
